Toward a Mechanistic Understanding of Inactivation of Respiratory Viruses in the Environment

Airborne transmission of most respiratory viruses was not widely acknowledged until the COVID-19 pandemic. For viruses to transmit between infected and healthy individuals, they must remain stable (i.e., "survive") in aerosols and droplets. Their stability is influenced by many factors including temperature, relative humidity (RH), physico-chemical properties of the carrier droplet, and virus strain. However, the exact mechanisms of viral inactivation remain unknown. The primary aim of this work was to delineate the complex interactions occurring within aerosols and droplets and the mechanisms that drive inactivation of viruses within them. Initially, we reviewed and synthesized existing studies on aerosols and droplets to identify knowledge gaps regarding these mechanisms. This system is highly complex, with various factors influencing viral stability interacting with each other. We recommend that future studies focus on more physiologically relevant aerosol and droplet sizes and fluids to better understand this system in real-world contexts. As previous studies often used large droplets, we shifted our focus to the environmental stability of enveloped viruses (Phi6, influenza virus, and SARS-CoV-2) as a function of initial droplet size (50, 5, and 1 µL) and evaporation kinetics. Our findings indicated that RH had a greater impact on viral decay in large droplets compared to small droplets, and in addition, suggested caution when using surrogates to study the stability of pathogenic viruses. Subsequently, we explored how gas-phase composition and pH affect influenza stability by manipulating the surrounding air. Results indicated that pH has little influence on influenza virus in saliva droplets, implying that another factor may drive decay. Lastly, we examined the survival of influenza virus in the presence of reactive oxygen species (ROS) scavengers, finding that certain ROS may play a significant role in virus inactivation.